Immunohistochemical prediction of brain metastases in patients with advanced breast cancer: the role of Rad51.
BACKGROUND
There are no clinically useful biomarkers predictive of brain metastases (BM) in breast cancer. In this study, we investigated the correlation between expression of selected proteins in the primary tumor and the risk of BM in patients with metastatic breast cancer (MBC).


METHODS
The study included 198 MBC patients (96 with and 102 without BM). Using tissue microarrays derived from the primary tumor, we assessed by immunohistochemical expression of ER, PR, HER2, Ki-67, CK5/6, EGFR, HER3, CXCR4, Rad51, E-cadherin, and claudin 3 and 4.


RESULTS
Ki-67 ≥14% (hazard ratio [HR] 2.76; P < 0.001), cytoplasmic expression of Rad51 (HR 1.87; P = 0.014) and ER-negativity (HR 1.72; P = 0.029) were associated with increased risk of BM in the multivariate analysis. A three-biomarker profile including ER, Ki-67 and Rad51 vs. other subtypes combined yielded an HR of 4.43 (P < 0.001).


CONCLUSIONS
ER-negativity, cytoplasmic expression of Rad51 and high Ki-67 are associated with increased risk of BM.
Regional Oncology Center, Aleja Zwycięstwa 31/32, Gdańsk 80-219, Poland. Electronic address: ksosna@gumed.edu.pl.
Katarzyna
K
Sosińska-Mielcarek
Renata
R
Duchnowska
Piotr
P
Winczura
Andrzej
A
Badzio
Hanna
H
Majewska
Joanna
J
Lakomy
Rafał
R
Pęksa
Beata
B
Pieczyńska
Barbara
B
Radecka
Sylwia
S
Dębska
Wojciech
W
Biernat
Jacek
J
Jassem
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology*; D015820:Cadherins / Q000032:analysis; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000556:secondary; D018275:Carcinoma, Lobular / Q000737:chemistry* / Q000556:secondary; D062465:Claudin-3 / Q000032:analysis; D062506:Claudin-4 / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053555:Keratin-5 / Q000032:analysis; D053553:Keratin-6 / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D051135:Rad51 Recombinase / Q000032:analysis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D020893:Receptor, ErbB-3 / Q000032:analysis; D019718:Receptors, CXCR4 / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012307:Risk Factors; D046888:Tissue Array Analysis; D055815:Young Adult
D014408:Biomarkers, Tumor; D015820:Cadherins; D062465:Claudin-3; D062506:Claudin-4; D053555:Keratin-5; D053553:Keratin-6; D019394:Ki-67 Antigen; D051135:Rad51 Recombinase; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D019718:Receptors, CXCR4; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C527276:CXCR4 protein, human; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human
Brain metastases; Breast cancer; Estrogen receptor; HER2; Ki-67; Rad51