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Authors Wu Z, Xu S, Zhou L, Yin W, Lin Y, Du Y, Wang Y, Jiang Y, Yin K, Zhang J, Lu J
Received 20 November 2017
Accepted for publication 10 January 2018
Published 15 February 2018 Volume 2018:11 Pages 801—808
DOI https://doi.org/10.2147/OTT.S157634
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 2
Editor who approved publication: Dr XuYu Yang
Background: The aims of this study were to determine whether the quantitative HER2 gene amplification level
is related to the key clinicopathological features that represent the aggressiveness
of breast cancer (BC) and to determine whether the quantitative HER2 gene amplification level
could predict the treatment response in the subset of HER2-positive patients
who received neoadjuvant targeted therapy.
Materials and
methods: Patients treated with weekly
cisplatin- and paclitaxel-based neoadjuvant chemotherapy, who had undergone
both immunohistochemistry and the fluorescence in situ hybridization test
for HER2 , were included in the study
(n=103). For HER2-positive patients, defined as immunohistochemistry score 3+
or fluorescence in situ hybridization ratio ≥2.0, trastuzumab was recommended
with neoadjuvant chemotherapy (n=45). Pathological complete response was
defined as complete pathological remission of tumor cells both in breast and
axillary lymph nodes postoperation.
Results: In all patients enrolled in the study, a higher HER2 amplification level was
significantly correlated with larger tumor size and the absence of ER and PR
expression. In HER2-positive patients treated with neoadjuvant trastuzumab
concurrent with chemotherapy, both univariate and multivariate logistic
regression showed that a higher HER2/CEP17 ratio
and HER2 gene copy number were
associated with a higher pathological complete response rate. When calculated
by receiver operating characteristics analysis, an optimal cutoff of 4.5 for
the HER2/CEP17 ratio was expected
to distinguish the most sensitive candidate for treatment with a combination of
trastuzumab and neoadjuvant chemotherapy.
Conclusion: A higher HER2 amplification
level was correlated with larger tumor size and reduced ER and PR expression,
which may indicate more aggressive tumor behavior. For HER2-positive patients,
the HER2/CEP17 ratio and HER2 gene copy number may be
good predictive factors for concurrent neoadjuvant trastuzumab and
chemotherapy.
Keywords: breast cancer, neoadjuvant, quantitative HER2 gene amplification,
pathological complete response, predictive