Prognostic markers in triple-negative breast cancer.
BACKGROUND
Triple-negative breast cancer (estrogen receptor-negative, progesterone receptor-negative, and HER2-negative) is a high risk breast cancer that lacks the benefit of specific therapy that targets these proteins.


METHODS
In this study, the authors examined a large and well characterized series of invasive breast carcinoma (n = 1944) with a long-term clinical follow-up (median, 56 months) by using tissue microarray. The series were also stained with concurrent immunohistochemical prognostic panels (estrogen receptor, progesterone receptor, HER-2, androgen receptor, epidermal growth factor receptor (EGFR), P-cadherin, E-cadherin, and basal (CK5/6, CK14), and p53), to characterize this specific subgroup of breast cancer and to identify prognostic markers that can identify tumors with more aggressive behavior.


RESULTS
Of informative cases, 16.3% were of the triple-negative phenotype. The majority of these tumors were grade 3, ductal/no-specific-type carcinomas. There were positive associations with larger size, pushing margins, poorer Nottingham Prognostic Index, development of recurrence and distant metastasis, and poorer outcome. In addition, associations were found with loss of expression of androgen receptor and E-cadherin, and positive expression of basal cytokeratins (basal phenotype), P-cadherin, p53, and EGFR. In all tumors, tumor size, lymph node stage, and androgen receptor were the most useful prognostic markers. In the lymph node-positive subgroup, both size and androgen receptor retained their prognostic significance. However, in the lymph node-negative tumors, basal phenotype was the sole prognostic marker identified in this subgroup. Other parameters including age, histological grade, tumor size, vascular invasion or other biomarkers included in the current study were not significant.


CONCLUSIONS
The authors concluded that assessment of androgen receptor and basal phenotype, in addition to the established pathologic variables, mainly lymph node status and tumor size, can be used to select high-risk and low-risk patients at the time of primary surgery and can provide valuable information on treatment options in these triple-negative tumors.
Rakha
Emad A
EA
Department of Histopathology, Molecular Medical Sciences, University of Nottingham, Nottingham, United Kingdom.
El-Sayed
Maysa E
ME
Green
Andrew R
AR
Lee
Andrew H S
AH
Robertson
John F
JF
Ellis
Ian O
IO
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000175:diagnosis*; D015820:Cadherins / Q000032:analysis; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis*; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D046228:Microarray Analysis; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D011944:Receptors, Androgen / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*
D014408:Biomarkers, Tumor; D015820:Cadherins; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D066246:ErbB Receptors