Discovery and preliminary confirmation of novel early detection biomarkers for triple-negative breast cancer using preclinical plasma samples from the Women's Health Initiative observational study.
Triple-negative breast cancer is a particularly aggressive and lethal breast cancer subtype that is more likely to be interval-detected rather than screen-detected. The purpose of this study is to discover and initially validate novel early detection biomarkers for triple-negative breast cancer using preclinical samples. Plasma samples collected up to 17 months before diagnosis from 28 triple-negative cases and 28 matched controls from the Women's Health Initiative Observational Study were equally divided into a training set and a test set and interrogated by a customized antibody array. Data were available on 889 antibodies; in the training set, statistically significant differences in case versus control signals were observed for 93 (10.5 %) antibodies at p < 0.05. Of these 93 candidates, 29 were confirmed in the test set at p < 0.05. Areas under the curve for these candidates ranged from 0.58 to 0.79. With specificity set at 98 %, sensitivity ranged from 4 to 68 % with 20 candidates having a sensitivity ≥ 20 % and 6 having a sensitivity ≥ 40 %. In an analysis of KEGG gene sets, the pyrimidine metabolism gene set was upregulated in cases compared to controls (p = 0.004 in the testing set) and the JAK/Stat signaling pathway gene set was downregulated (p = 0.003 in the testing set). Numerous potential early detection biomarkers specific to triple-negative breast cancer in multiple pathways were identified. Further research is required to followup on promising candidates in larger sample sizes and to better understand their potential biologic importance as our understanding of the etiology of triple-negative breast cancer continues to grow.
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. cili@fhcrc.org
Christopher I
CI
Li
Justin E
JE
Mirus
Yuzheng
Y
Zhang
Arturo B
AB
Ramirez
Jon J
JJ
Ladd
Ross L
RL
Prentice
Martin W
MW
McIntosh
Samir M
SM
Hanash
Paul D
PD
Lampe
D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000378:metabolism; D016022:Case-Control Studies; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D040081:Protein Array Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012680:Sensitivity and Specificity; D016387:Women's Health
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human