Early versus late distant metastasis and adjuvant chemotherapy alone versus both radiotherapy and chemotherapy in molecular apocrine breast cancer

Abstract

As a new subtype of breast cancer, molecular apocrine breast cancer (MABC) is estrogen receptor (ER) and progesterone receptor (PR) negative expression, but androgen receptor (AR) positive expression. The prognostic significance and clinical biological behavior of MABC have remained unclear up to now. This study aimed to analysis the distant metastasis behavior and response to adjuvant radiotherapy and chemotherapy of MABC subgroup. The report showed that there were significant differences between early and late distant metastasizing tumors with respect to Ki67, epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF) expressions by a retrospective analysis consisting of 410 invasive breast cancer patients, which included 205 MABC and 205 nonMABC cases. MABC subgroup metastasized earlier than nonMABC subgroup, and MABC showed a tendency for a higher metastasis rate in lung, liver and brain, but lower in bone. HER2-positive or VEGF-positive tumors were more inclined to develop bone metastasis within MABC subgroup. The survival rate was superior for patients undergone both adjuvant radiotherapy and chemotherapy than those undergone chemotherapy alone in nonMABC subgroup, but there was no significant difference in MABC subgroup. Our data suggested that MABC subgroup seemed to develop distant metastasis earlier than nonMABC subgroup, and patients with MABC indicated poor prognosis. This study might also provide a foundation for helping patients receive reasonable treatments according to molecular subtype.

Keywords: Pathology Section; androgen receptor; distant metastasis; molecular apocrine breast cancer; radiotherapy and chemotherapy; survival rate.

Figure 1. Location of immunohistochemical staining of each protein marker in invasive breast cancer tissues

Immunohistochemical staining of estrogen receptor (ER) revealed nuclear staining A., progesterone receptor (PR) revealed nuclear staining B., androgen receptor (AR) revealed nuclear staining C., epidermal growth factor receptor 2 (HER2) revealed cytomembrane staining D., Ki67 revealed nuclear staining E., p53 revealed nuclear staining F. and vascular endothelial growth factor (VEGF) revealed cytoplasm staining G.; HE staining H. of invasive breast cancer tissues. Original magnification ×200.

Figure 2. A tumor classified as carcinomas with apocrine differentiation, which had the immunohistochemical characteristics of molecular apocrine breast cancer (MABC)

A., B. and C. Immunohistochemical staining of ER (negative), PR (negative) and AR (positive) in carcinomas with apocrine differentiation. D. HE staining of carcinomas with apocrine differentiation. a and b. Positive controls for ER and PR. Original magnification ×200. (Bar = 80μm)

Figure 3. The expression of VEGF was significantly different between MABC and nonMABC subgroups, and patients with MABC indicated poor prognosis than nonMABC subgroup

A. There was significant difference between VEGF positive expression and MABC subgroup (χ² = 9.333, P = 0.002). B., C. and D.. Distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) curves of 410 patients were generated according to the Kaplan-Meier method.

Figure 4. Patients undergone both adjuvant radiotherapy and chemotherapy had relative better outcome than those undergone chemotherapy alone within nonMABC subgroup, but there was no significant difference in MABC subgroup

A., B. and C.. DMFS, DFS and OS curves of 184 MABC patients undergone both radiotherapy and chemotherapy or chemotherapy alone were generated according to the Kaplan-Meier method. D., E. and F.. DMFS, DFS and OS curves of 190 nonMABC patients undergone both radiotherapy and chemotherapy or chemotherapy alone were generated according to the Kaplan-Meier method.