Biology Reference
In-Depth Information
CEA is a circulating tumor marker that is used as a prognostic marker as well as a mecha-
nism to monitor recurrence. However, the poor sensitivity of CEA makes it less than ideal [165] .
Several investigators have examined the potential role of circulating miRNAs as diagnostic
markers for breast cancer, and most of this work has emerged in the last two years. Changes in
circulating miRNA expression levels have been associated with tumorigenesis, prognosis, and
response to therapy.
Schrauder and coworkers evaluated the expression of 240 miRNAs in whole blood of 48
early-stage breast cancer patients and 57 healthy controls, and reported that miR-202 was
differentially expressed between the two groups [166] . Zhao et  al. examined plasma miR-
NAs in 93 breast cancer patients who previously received neoadjuvant chemotherapy, and
32 healthy volunteers [167] . Using a cohort of serum from 102 pre-operative breast cancer
patients, 34 post-operative samples, 32 with benign breast disease, and 53 healthy controls,
Schwarzenbach and coworkers showed that miR-20a and miR-21 were expressed at higher
levels in women with breast cancer and benign disease compared to healthy women [168] .
However, only miR-214 was able to distinguish breast cancer from benign disease and
controls, with an AUC of 0.878 and 0.883, respectively. Furthermore, miR-214 levels were
reduced in post-operative sera. miR-214 has been shown to target PTEN tumor suppressor
gene [169] . Van Schooneveld et  al. selected the most differentially expressed miRNAs after
examination of 84 breast cancer and eight normal breast tissues, and analyzed serum from 75
breast cancer patients and 20 healthy controls [170] . The study revealed that miR-215, miR-
411, and miR-299 were differentially expressed between sera from healthy controls and that
from patients with untreated metastatic breast cancer.
The ability of miRNAs to predict therapy response has been recently evaluated in breast
cancer. Specifically, Jung et al. evaluated plasma miRNA expression in breast cancer patients
who received neoadjuvant trastuzumab-based chemotherapy including 18 with complete
response and 11 with residual disease, in addition to 39 pre-operative and 30 post-operative
sera from breast cancer patients who did not receive neoadjuvant therapy [171] . Their find-
ings revealed that miR-210 was expressed at higher levels in patients with residual disease
than those with a complete response. In addition, miR-210 was higher in pre- and post-sur-
gery in patients with lymph node involvement, suggesting that miR-210 could be used as
a biomarker to predict response to trastuzumab-based therapy. In another study, Zhao et al.
found that miR-221 was significantly associated with hormone receptor status, with high
miR-221 expression being associated with negative hormone receptor status [167] . These
studies suggested that miR-221 could be a useful predictive biomarker for neoadjuvant
chemotherapy. miR-122 and miR-375 were also revealed as predictive markers of neoadju-
vant chemotherapy in a study by Wu et al. that examined pre-treatment sera from 42 breast
cancer patients with stage II and III disease, and validated the findings in an independent set
of 26 sera samples [172] .
In yet another predictive miRNA study, Wang and coworkers showed that high expres-
sion of miR-125b in serum of 56 breast cancer patients treated with neoadjuvant therapy was
associated with poor response in 26 patients [173] . This high expression of miR-125b was also
associated with a lower apoptotic rate and a higher percentage of proliferating cells. One of
the largest studies in circulating miRNAs in breast cancer is that of Cuk et al., who examined
plasma from 80 healthy controls and 127 sporadic breast cancer cases, and found that miR-
148b, miR-376c, miR-409-3p, and miR-801 were significantly up-regulated in plasma from
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