Immunohistochemical Ki67 after short-term hormone therapy identifies low-risk breast cancers as reliably as genomic markers
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Takayuki Iwamoto1,2, Toyomasa Katagiri3, Naoki Niikura4, Yuichiro Miyoshi1, Mariko Kochi1,2, Tomohiro Nogami1, Tadahiko Shien1, Takayuki Motoki1,2, Naruto Taira1, Masako Omori5, Yutaka Tokuda4, Toshiyoshi Fujiwara2, Hiroyoshi Doihara1, Balazs Gyorffy6,7, Junji Matsuoka1,2,8
1Department of Breast and Endocrine Surgery, Okayama University Hospital, Okayama, Japan
2Department of Gastroenterological Surgery, Okayama University Hospital, Okayama, Japan
3Division of Genome Medicine, Institute for Genome Research, Tokushima University, Tokushima, Japan
4Department of Breast and Endocrine Surgery, Tokai University School of Medicine, Kanagawa, Japan
5Department of Pathology, Okayama University Hospital, Okayama, Japan
6MTA TTK Lendület Cancer Biomarker Research Group, Budapest, Hungary
72nd Department of Pediatrics, Semmelweis University, Budapest, Hungary
8Department of Palliative and Supportive Medicine, Okayama University Hospital, Okayama, Japan
Takayuki Iwamoto, email: firstname.lastname@example.org
Keywords: short-term hormone therapy, IHC Ki67, genomic marker, breast cancer
Received: June 29, 2016 Accepted: January 31, 2017 Published: February 16, 2017
Background: The purpose of this study was to test whether immunohistochemical (IHC) Ki67 levels after short-term preoperative hormone therapy (post-Ki67) predict similar numbers of patients with favorable prognoses as genomic markers.
Results: Thirty paired cases (60 samples) were enrolled in this study. Post-Ki67 levels were significantly lower than pre-treatment Ki67 levels (P < 0.001). Post-Ki67 predicted more low-risk cases (83.3%, 25/30) than pre-genomic surrogate signature(GSS) (66.7%: 20/30), but the difference in predictive power was not significant (P = 0.233). Proliferation (MKI67, STK15, Survivin, CCNB1, and MYBL2) and estrogen (ER, PGR, BCL2, and SCUBE2) related signatures were significantly downregulated after therapy (P < 0.001 and 0.041, respectively).
Materials and Methods: Core needle biopsy specimens of primary breast cancer were collected at Okayama University Hospital from hormone receptor-positive and human epidermal growth factor 2-negative patients that subsequently received two weeks of neoadjuvant hormone therapy. Paired post-treatment specimens from surgical samples were also collected. IHC Ki67 levels and GSS were compared between pre- and post-hormone treatment samples. Changes of gene expression pattern in short-term hormone therapy were also assessed.
Conclusions: IHC based post-Ki67 levels may have distinct predictive power compared with the naïve IHC Ki67. Future studies with larger cohorts and longer follow-up periods may be needed to validate our results.
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