title: Amplification patterns of three genomic regions predict distant recurrence in breast carcinoma.
abstract: 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.
authors.affiliation: Exagen Diagnostics, Albuquerque, NM, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Davis
authors.forename: Cole
authors.initials: C
authors.lastname: Harris
authors.forename: Lei
authors.initials: L
authors.lastname: Tang
authors.forename: Patti
authors.initials: P
authors.lastname: Doherty
authors.forename: Peter
authors.initials: P
authors.lastname: Hraber
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Sakai
authors.forename: Therese
authors.initials: T
authors.lastname: Bocklage
authors.forename: Katie
authors.initials: K
authors.lastname: Doeden
authors.forename: Bryan
authors.initials: B
authors.lastname: Hall
authors.forename: John
authors.initials: J
authors.lastname: Alsobrook
authors.forename: Ian
authors.initials: I
authors.lastname: Rabinowitz
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Williams
authors.forename: John
authors.initials: J
authors.lastname: Hozier
mesh_terms: 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
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone