DNA repair protein biomarkers associated with time to recurrence in triple-negative breast cancer.
OBJECTIVE
To evaluate the prognostic utility of immunohistochemical assessment of key proteins in multiple DNA repair pathways in triple-negative breast cancer (TNBC; estrogen receptor negative, progesterone receptor negative, and HER2/neu negative by immunohistochemistry).


METHODS
Archived clinically annotated tumor specimens from 112 women with TNBC were immunostained with antibodies against DNA repair proteins and scored using digital image analysis. The cohort was divided into training and test sets for development of a multiantibody model. Scores were combined with clinical data to assess association with outcome.


RESULTS
Low XPF (P = 0.005), pMK2 (P = 0.01), MLH; P = 0.002), and FANCD2 (P = 0.001) were each associated with shorter time to recurrence (TTR) in univariate analysis. A 4-antibody model could segregate high-risk and low-risk groups on the basis of TTR in both the training (relative risk [RR] = 3.52; P = 9.05E-07) and test (RR 2.67; P = 0.019) cohorts.


CONCLUSIONS
DNA repair proteins may be useful as prognostic markers in TNBC. Further study in larger, uniformly treated cohorts with additional clinical parameters is warranted.
Dana Farber/Brigham and Women's Cancer Center Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts, USA.
Brian M
BM
Alexander
Kam
K
Sprott
D Allan
DA
Farrow
XiaoZhe
X
Wang
Alan D
AD
D'Andrea
Stuart J
SJ
Schnitt
Laura C
LC
Collins
David T
DT
Weaver
Judy E
JE
Garber
D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D004260:DNA Repair / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012008:Recurrence; D012189:Retrospective Studies; D013997:Time Factors
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone