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27.08.2018 | Preclinical study | Ausgabe 2/2018

Breast Cancer Research and Treatment 2/2018

Therapeutic predictors of neoadjuvant endocrine therapy response in estrogen receptor-positive breast cancer with reference to optimal gene expression profiling

Breast Cancer Research and Treatment > Ausgabe 2/2018
Lisa Goto-Yamaguchi, Mutsuko Yamamoto-Ibusuki, Yutaka Yamamoto, Yoshitaka Fujiki, Mai Tomiguchi, Aiko Sueta, Takashi Takeshita, Hirotaka Iwase
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s10549-018-4933-5) contains supplementary material, which is available to authorized users.



Neoadjuvant endocrine therapy (NAET) for estrogen receptor-positive primary breast cancer causes adequate tumor shrinkage, and is expected to be helpful for breast-conserving surgery, but the adaptation criteria, especially in regard to treatment duration, have never been elucidated. Re-visiting past gene expression profiles, we explored the data for specialized pre-therapeutic predictors and validated the results using our in-house clinical cohorts.


We sorted the genes related to a > 30% tumor volume reduction through NAET from a cDNA microarray data-set of GSE20181, then selected the top 40 genes. We validated these gene expression levels using pre-therapeutic biopsy samples obtained from patients treated with long-term NAET (over 4 months; N = 40). A short-term (2–8 weeks; N = 37) NAET cohort was also validated to clarify whether expression of these genes is also related to a rapid response of Ki67 and PEPI score.


In the long-term group, higher expression of KRAS, CUL2, FAM13A, ADCK2, and LILRA2 was significantly associated with tumor shrinkage, and KRAS, MMS19, and IVD were related to lower PEPI score (≤ 3). Meanwhile in the short-term group, none of these genes except CUL2 showed a direct correlation with Ki67 reduction or PEPI score. This suggested that tumor shrinkage by NAET might be induced by response to the hypoxic environment (CUL2, FAM13A, KRAS) and activation of tumor immune system (LILRA2), without involving inhibition of proliferation.


Expression of specific genes may allow selection of the most responsive patients for maximum tumor shrinkage with NAET.

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Supplementary material 1 (DOC 56 KB)
Supplementary material 2 (DOC 626 KB)
Supplementary material 3 (DOC 158 KB)
Supplementary material 4 (DOC 52 KB)
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