Abstract
BackgroundInvasive micropapillary carcinoma of the breast (IMPC) is a histological tumor variant that occurs with 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 (HER2) 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.MethodsWe retrospectively studied 86 HER2-positive breast cancer patients treated with trastuzumab and chemotherapy 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.ResultsIMPC, 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 and 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, was strongly expressed in all IMPC cases tested. IMPC appeared as the histological breast cancer subtype with the highest MUC4 expression compared to IDC, lobular and mucinous carcinoma.ConclusionIn HER2-positive breast cancer, the presence of IMPC should be carefully examined. As it is often not informed, because it is relatively difficult to identify or altogether overlooked, we propose MUC4 expression as a useful biomarker to highlight IMPC presence. Patients with MUC4-positive tumors with IMPC component should be more frequently monitored and/or receive additional therapies.
Highlights
Invasive micropapillary carcinoma of the breast (IMPC) is a histological tumor variant that occurs with low frequency characterized by an inside-out formation of tumor clusters with a pseudopapillary arrangement
IMPC is associated with poor outcome in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients As HER-2 expression is frequently observed in IMPC [8], our purpose was to study the incidence and clinical relevance of this histological breast cancer subtype in HER-2 positive breast cancer patients
We found that 16 tumors (18.6% of the HER-2-positive tumors) were either pure (6 cases) or had different proportions of IMPC component mixed with invasive ductal carcinoma (IDC) (IMPC 10–30%:4 cases; 31–70%: 2 cases; 71–90%: 4 cases)
Summary
Invasive micropapillary carcinoma of the breast (IMPC) is a histological tumor variant that occurs with low frequency characterized by an inside-out formation of tumor clusters with a pseudopapillary arrangement. Invasive micropapillary carcinoma of the breast (IMPC) is defined as a low-frequent tumor variant of invasive carcinomas characterized by a unique inside-out formation of tumor clusters with a pseudopapillary arrangement that is present in ~6% of all breast cancers [1, 2]. IMPC has an angioinvasive phenotype that allows its spread into blood vessels, which leads to higher rates of lymph node metastasis and poor clinical outcome [5, 6] This histological entity is more likely to present human epidermal growth factor receptor-2 (HER2) and estrogen receptor (ER) expression [5, 7, 8]. A sensitive biomarker become instrumental in revealing its presence
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