Amplification patterns of three genomic regions predict distant recurrence in breast carcinoma.
Currently used clinical and histopathological parameters imprecisely define the risk of distant recurrence in breast cancer, underscoring the need for more informative prognostic markers. In the present fluorescence in situ hybridization study of archived surgical specimens, we derived an algorithm for computing a prognostic index (PI) from DNA copy numbers of three genomic regions (CYP24, PDCD6IP, and BIRC5) for estrogen/progesterone receptor-positive (ER/PR+) cancers and a distinct PI (based on NR1D1, SMARCE1, and BIRC5) for estrogen/progesterone receptor-negative (ER/PR-) cancers. Among independent test cases stratified by PI, recurrence rates were significantly higher among high-risk patients than low-risk patients for both ER/PR+ (odds ratio = 9.52, 95% confidence interval >2.12, P = 0.0024) and ER/PR- (odds ratio = 12.3, 95% confidence interval >1.45, P = 0.0188) cancers. Among the entire population, recurrences were significantly more prevalent for cases with PI above the medians for both ER/PR+ (Fisher's exact, P = 1.19 x 10(-5)) and ER/PR- (P = 0.0025) patients and for the node-negative subsets (ER/PR+ node-negative, P = 0.042 and ER/PR- node-negative, P = 0.039). In conclusion, these markers perform well in comparison with other criteria for recurrence risk assessment and can be used with routinely formalin-fixed, paraffin-embedded surgical specimens.
Davis
Lisa M
LM
Exagen Diagnostics, Albuquerque, NM, USA.
Harris
Cole
C
Tang
Lei
L
Doherty
Patti
P
Hraber
Peter
P
Sakai
Yumiko
Y
Bocklage
Therese
T
Doeden
Katie
K
Hall
Bryan
B
Alsobrook
John
J
Rabinowitz
Ian
I
Williams
Thomas M
TM
Hozier
John
J
D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D018628:Gene Dosage; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D012008:Recurrence
D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone