Prognostic significance of tumor grading and staging in mammary carcinomas with neuroendocrine differentiation

Invasive mammary carcinoma with neuroendocrine differentiation has been controversial in terms of its definition and clinical outcome. In 2003, the World Health Organization histologic classification of tumors designated this entity as neuroendocrine carcinoma of the breast and defined mammary neuroendocrine carcinoma as expression of neuroendocrine markers in more than 50% of tumor cells. It is an uncommon neoplasm. Our recent study showed that it is a unique clinicopathologic entity and has a poor clinical outcome compared with invasive mammary carcinoma with similar pathologic stage. Other investigators have also demonstrated a different molecular profile in this type of tumor from that of invasive ductal carcinoma. It is unknown whether the current prognostic markers for invasive mammary carcinoma are also applicable for neuroendocrine carcinoma of the breast. In the current study, we reviewed the clinicopathologic features and outcome data in 74 cases of mammary neuroendocrine carcinoma from the surgical pathology files at The University of Texas, MD Anderson Cancer Center, to identify relevant prognostic markers for this tumor type. As shown previously by univariate analysis, large tumor size, high nuclear grade, and presence of regional lymph node metastasis are adverse prognostic factors for overall survival and distant recurrence-free survival. In the current study, multivariate analysis revealed that overall survival was predicted by tumor size, lymph node status, and proliferation rate as judged by Ki-67 immunohistochemistry. Only nodal status proved to be a significant independent prognostic factor for distant recurrence-free survival. Neither mitosis score nor histologic grade predicted survival in mammary neuroendocrine carcinoma. Our data suggest that routine evaluation of Ki-67 proliferation index in these unusual tumors may provide more valuable information than mitotic count alone.