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Takayuki Iwamoto
Department Kawasaki Medical School Kawasaki Medical School, Department of Breast and Thyroid Surgery, Position Assistant Professor |
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| Article types | 原著 |
| Language | English |
| Peer review | Peer reviewed |
| Title | Subtype-Specific Metagene-Based Prediction of Outcome after Neoadjuvant and Adjuvant Treatment in Breast Cancer. |
| Journal | Formal name：Clinical cancer research : an official journal of the American Association for Cancer Research Abbreviation：Clin Cancer Res ISSN code：15573265/10780432 |
| Domestic / Foregin | Foregin |
| Volume, Issue, Page | 22(2),pp.337-45 |
| Author and coauthor | Maurizio Callari, Vera Cappelletti, Francesca D'Aiuto, Valeria Musella, Antonio Lembo, Fabien Petel, Thomas Karn, Takayuki Iwamoto, Paolo Provero, Maria Grazia Daidone, Luca Gianni, Giampaolo Bianchini |
| Publication date | 2016/01 |
| Summary | PURPOSE:In spite of improvements of average benefit from adjuvant/neoadjuvant treatments, there are still individual patients with early breast cancer at high risk of relapse. We explored the association with outcome of robust gene cluster-based metagenes linked to proliferation, ER-related genes, and immune response to identify those high-risk patients.EXPERIMENTAL DESIGN:A total of 3,847 publicly available gene-expression profiles were analyzed (untreated, N = 826; tamoxifen-treated, N = 685; chemotherapy-treated, N = 1,150). Genes poorly performing in formalin-fixed samples were removed. Outcomes of interest were pathologic-complete response (pCR) and distant metastasis-free survival (DMFS). In ER(+)HER2(-), the proliferation and ER-related metagenes were combined to define three risk groups. In HER2(+) and ER(-)HER2(-) risk groups were defined by tertiles of an immune-related metagene.RESULTS:The high-proliferation/low-ER group of ER(+)HER2(-) breast cancer had significantly higher pCR rate [OR, 5.01 (1.76-17.99), P = 0.005], but poorer outcome [HR = 3.73 (1.63-8.51), P = 0.0018] than the low-proliferation/high-ER. A similar association with outcome applied to patients with residual disease (RD) after neoadjuvant chemotherapy (P = 0.01). In ER(-)HER2(-) and HER2(+) breast cancer, immune metagene in the high tertile was linked to higher pCR [33.7% vs. 11.6% in high and low tertile, respectively; OR, 3.87 (1.79-8.95); P = 0.0009]. In ER(-)HER2(-), after adjuvant/neoadjuvant chemotherapy, 5-year DMFS was 85.4% for high-tertile immune metagene, and 43.9% for low tertile. The outcome association was similar in patients with RD (P = 0.0055). In HER2(+) breast cancer treated with chemotherapy the association with risk of relapse was not significant.CONCLUSIONS:We developed metagene-based predictors able to define low and high risk of relapse after adjuvant/neoadjuvant therapy. High-risk patients so defined should be preferably considered for trials with investigational |
| DOI | 10.1158/1078-0432.CCR-15-0757 |
| PMID | 26423797 |